Validation of CT radiomics for prediction of distant metastasis after surgical resection in patients with clear cell renal cell carcinoma: exploring the underlying signaling pathways

To develop a radiomics model using preoperative multiphasic CT for predicting distant metastasis after surgical resection in patients with localized clear cell renal cell carcinoma (ccRCC) and to identify key biological pathways underlying the predictive radiomics features using RNA sequencing data. In this multi-institutional retrospective study, a CT radiomics metastasis score (RMS) was developed from a radiomics analysis cohort (n = 184) for distant metastasis prediction. Using a gene expression analysis cohort (n = 326), radiomics-associated gene modules were identified. Based on a radiogenomics discovery cohort (n = 42), key biological pathways were enriched from the gene modules. Furthermore, a multigene signature associated with RMS was constructed and validated on an independent radiogenomics validation cohort (n = 37). The 9-feature-based RMS predicted distant metastasis with an AUC of 0.861 in validation set and was independent with clinical factors (p < 0.001). A gene module comprising 114 genes was identified to be associated with all nine radiomics features (p < 0.05). Four enriched pathways were identified, including ECM-receptor interaction, focal adhesion, protein digestion and absorption, and PI3K-Akt pathways. Most of them play important roles in tumor progression and metastasis. A 19-gene signature was constructed from the radiomics-associated gene module and predicted metastasis with an AUC of 0.843 in the radiogenomics validation cohort. CT radiomics features can predict distant metastasis after surgical resection of localized ccRCC while the predictive radiomics phenotypes may be driven by key biological pathways related to cancer progression and metastasis. • Radiomics features from primary tumor in preoperative CT predicted distant metastasis after surgical resection in patients with localized ccRCC. • CT radiomics features predictive of distant metastasis were associated with key signaling pathways related to tumor progression and metastasis. • Gene signature associated with radiomics metastasis score predicted distant metastasis in localized ccRCC.